Jump to content

HLA-DO: Difference between revisions

Edit links
From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
No edit summary
No edit summary
Line 37: Line 37:
| LocusSupplementaryData =
| LocusSupplementaryData =
}}
}}
'''Human leukocyte histocompatibility complex DO (HLA-DO)''' is an intracellular, [[Protein dimer|dimeric]] non-classical [[Major Histocompatibility Complex]] (MHC) [[MHC class II|Class II]] [[protein]] composed of [[HLA-DOA|α-]] and [[HLA-DOB|β]]-subunits which interact with [[HLA-DM]] in order to fine tune [[Immunodominance|immunodominant]] [[epitope]] selection.<ref name="Kuby_2013">{{cite book | title = Kuby immunology | vauthors = Owen JA, Punt J, Stranford SA, Jones PP, Kuby J | date = 2013 | publisher = W.H. Freeman | isbn = 978-1-4641-1991-0 | edition = 7th | location = New York | oclc = 820117219}}</ref> As a non-classical MHC Class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in [[Antigen|antigenic]] peptide [[Chaperone (protein)|chaperoning]] and loading, as opposed to it classical counterparts, which are [[Polymorphism (biology)|polymorphic]] and involved in antigen presentation.<ref name="Poluektov_2013">{{cite journal | vauthors = Poluektov YO, Kim A, Sadegh-Nasseri S | title = HLA-DO and Its Role in MHC Class II Antigen Presentation | journal = Frontiers in Immunology | volume = 4 | pages = 260 | date = September 2013 | pmid = 24009612 | pmc = 3756479 | doi = 10.3389/fimmu.2013.00260 }}</ref> Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body, namely, the exclusive expression of HLA-DO in [[B cell|B cells]], [[Thymus|thymic medullary epithelial cells]], and [[Dendritic cell|dendritic cells]] suggests that it may be of physiological importance and has inspired further research.<ref name="Poluektov_2013" /> Moreover, HLA-DO is stable in complex with HLA-DM, and its exhibited instability in the absence of HLA-DM, as well as its evolutionary conservation, further denote its biological significance and potential to confer evolutionary benefits to its host.<ref name="Chen_2003">{{cite journal | vauthors = Chen X, Jensen PE | title = The expression of HLA-DO (H2-O) in B lymphocytes | journal = Immunologic Research | volume = 29 | issue = 1–3 | pages = 19-28 | date = June 2004 | pmid = 15181267 | doi = 10.1385/IR:29:1-3:019 }}</ref><ref name=":0">{{Cite journal|last=Adler|first=Lital N.|last2=Jiang|first2=Wei|last3=Bhamidipati|first3=Kartik|last4=Millican|first4=Matthew|last5=Macaubas|first5=Claudia|last6=Hung|first6=Shu-chen|last7=Mellins|first7=Elizabeth D.|date=2017-03-23|title=The Other Function: Class II-Restricted Antigen Presentation by B Cells|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362600/|journal=Frontiers in Immunology|volume=8|doi=10.3389/fimmu.2017.00319|issn=1664-3224|pmc=PMC5362600|pmid=28386257}}</ref>
'''Human leukocyte histocompatibility complex DO (HLA-DO)''' is an intracellular, [[Protein dimer|dimeric]] non-classical [[Major Histocompatibility Complex]] (MHC) [[MHC class II|Class II]] [[protein]] composed of [[HLA-DOA|α-]] and [[HLA-DOB|β]]-subunits which interact with [[HLA-DM]] in order to fine tune [[Immunodominance|immunodominant]] [[epitope]] selection.<ref name="Kuby_2013">{{cite book | title = Kuby immunology | vauthors = Owen JA, Punt J, Stranford SA, Jones PP, Kuby J | date = 2013 | publisher = W.H. Freeman | isbn = 978-1-4641-1991-0 | edition = 7th | location = New York | oclc = 820117219}}</ref> As a non-classical MHC Class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in [[Antigen|antigenic]] peptide [[Chaperone (protein)|chaperoning]] and loading, as opposed to it classical counterparts, which are [[Polymorphism (biology)|polymorphic]] and involved in antigen presentation.<ref name="Poluektov_2013">{{cite journal | vauthors = Poluektov YO, Kim A, Sadegh-Nasseri S | title = HLA-DO and Its Role in MHC Class II Antigen Presentation | journal = Frontiers in Immunology | volume = 4 | pages = 260 | date = September 2013 | pmid = 24009612 | pmc = 3756479 | doi = 10.3389/fimmu.2013.00260 }}</ref><ref name=":1">{{Cite journal|last=Yin|first=Liusong|last2=Stern|first2=Lawrence J.|date=2013-10-17|title=HLA-DM Focuses on Conformational Flexibility Around P1 Pocket to Catalyze Peptide Exchange|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3797982/|journal=Frontiers in Immunology|volume=4|doi=10.3389/fimmu.2013.00336|issn=1664-3224|pmc=PMC3797982|pmid=24146666}}</ref> Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body, namely, the exclusive expression of HLA-DO in [[B cell|B cells]], [[Thymus|thymic medullary epithelial cells]], and [[Dendritic cell|dendritic cells]] suggests that it may be of physiological importance and has inspired further research.<ref name="Poluektov_2013" /><ref name=":2">{{Cite journal|last=Denzin|first=Lisa K.|date=2013-12-17|title=Inhibition of HLA-DM Mediated MHC Class II Peptide Loading by HLA-DO Promotes Self Tolerance|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865790/|journal=Frontiers in Immunology|volume=4|doi=10.3389/fimmu.2013.00465|issn=1664-3224|pmc=PMC3865790|pmid=24381574}}</ref> Moreover, HLA-DO is stable in complex with HLA-DM, and its exhibited instability in the absence of HLA-DM, as well as its evolutionary conservation, further denote its biological significance and potential to confer evolutionary benefits to its host.<ref name="Chen_2003">{{cite journal | vauthors = Chen X, Jensen PE | title = The expression of HLA-DO (H2-O) in B lymphocytes | journal = Immunologic Research | volume = 29 | issue = 1–3 | pages = 19-28 | date = June 2004 | pmid = 15181267 | doi = 10.1385/IR:29:1-3:019 }}</ref><ref name=":0">{{Cite journal|last=Adler|first=Lital N.|last2=Jiang|first2=Wei|last3=Bhamidipati|first3=Kartik|last4=Millican|first4=Matthew|last5=Macaubas|first5=Claudia|last6=Hung|first6=Shu-chen|last7=Mellins|first7=Elizabeth D.|date=2017-03-23|title=The Other Function: Class II-Restricted Antigen Presentation by B Cells|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362600/|journal=Frontiers in Immunology|volume=8|doi=10.3389/fimmu.2017.00319|issn=1664-3224|pmc=PMC5362600|pmid=28386257}}</ref>


== Discovery ==
== Discovery ==
Line 43: Line 43:


== Function ==
== Function ==
Functionally, HLA-DO is believed to be negative modulator of HLA-DM; the binding of HLA-DO at the MHC Class II peptide-exchange [[catalysis]] site demonstrate that it acts as a [[Competitive inhibition|competitive inhibitor]].<ref name="Kuby_2013" /><ref name="Chen_2003" />
Functionally, HLA-DO is believed to be negative modulator of HLA-DM; the binding of HLA-DO at the MHC Class II peptide-exchange [[catalysis]] site demonstrate that it acts as a [[Competitive inhibition|competitive inhibitor]].<ref name="Kuby_2013" /><ref name="Chen_2003" /><ref name=":2" />


During infection, [[Exogenous bacteria|exogenous]] antigen is internalized by [[phagocytosis]] or [[receptor-mediated endocytosis]], and processed in hydrolytic enzyme-containing compartments of increasing acidity.<ref name="Kuby_2013" /><ref name=":0" /> Once the degraded antigen is 13-18 residues, it is ready to bind to MHC Class II molecules, which ultimately presents the antigen to [[T cell|T cells]] and class III molecules and progresses the immune response.<ref name="Kuby_2013" /> To bind to the MHC-Class II protein, HLA-DM catalyzes the exchange of [[CLIP protein|CLIP,]] a protein occupying the binding groove of MHC Class II, with the antigenic [[oligopeptide]].<ref name="Kuby_2013" /><ref name=":0" /> HLA-DO remains strongly associates with HLA-DM throughout the catalyzed exchange.<ref name="Poluektov_2013" />
During infection, [[Exogenous bacteria|exogenous]] antigen is internalized by [[phagocytosis]] or [[receptor-mediated endocytosis]], and processed in hydrolytic enzyme-containing compartments of increasing acidity.<ref name="Kuby_2013" /><ref name=":0" /> Once the degraded antigen is 13-18 residues, it is ready to bind to MHC Class II molecules, which ultimately presents the antigen to [[T cell|T cells]] and class III molecules and progresses the immune response.<ref name="Kuby_2013" /> To bind to the MHC-Class II protein, HLA-DM catalyzes the exchange of [[CLIP protein|CLIP,]] a protein occupying the binding groove of MHC Class II, with the antigenic [[oligopeptide]].<ref name="Kuby_2013" /><ref name=":0" /> HLA-DO remains strongly associates with HLA-DM throughout the catalyzed exchange.<ref name="Poluektov_2013" />


== Structure ==
== Structure ==
Before the three-dimensional structure of complexed HLA-DO was elucidated by [[X-ray crystallography]], its crystal structure was modeled after [[Homology (biology)|homology]] studies to classical MHC Class II proteins.<ref name=":0" /> Following crystallization of the protein, HLA-DO was found to be conformationally similar to classical MHC Class II protein, with alterations in the [[N-terminus]].<ref name="Mellins_2913" /> The structure of the free HLA-DO protein, however, remains to be elucidated.<ref name="Mellins_2913" />
Before the three-dimensional structure of complexed HLA-DO was elucidated by [[X-ray crystallography]], its crystal structure was modeled after [[Homology (biology)|homology]] studies to classical MHC Class II proteins.<ref name=":1" /><ref name=":0" /><ref name=":3">{{Cite journal|last=Pos|first=Wouter|last2=Sethi|first2=Dhruv K.|last3=Wucherpfennig|first3=Kai W.|date=2013-10|title=Mechanisms of Peptide Repertoire Selection by HLA-DM|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3796002/|journal=Trends in immunology|volume=34|issue=10|pages=495–501|doi=10.1016/j.it.2013.06.002|issn=1471-4906|pmc=PMC3796002|pmid=23835076}}</ref> Following crystallization of the protein, HLA-DO was found to be conformationally similar to classical MHC Class II protein, with alterations in the [[N-terminus]].<ref name=":1" /><ref name="Mellins_2913" /><ref name=":3" /> The structure of the free HLA-DO protein, however, remains to be elucidated.<ref name="Mellins_2913" />


== References ==
== References ==

Revision as of 21:27, 7 March 2018

Major Histocompatibility Complex, Class II, DO alpha
Identifiers
SymbolHLA-DOA
Alt. symbolsHLA-DZA, HLA-DNA
NCBI gene3111
HGNC4936
OMIM142930
RefSeqNM_002119
UniProtQ9TQD3
Other data
LocusChr. 6 p21.3
Search for
StructuresSwiss-model
DomainsInterPro
Major Histocompatibility Complex, Class II, DO beta
Identifiers
SymbolHLA-DOB
NCBI gene3112
HGNC4937
OMIM600629
RefSeqNM_002120
UniProtP13765
Other data
LocusChr. 6 p21.3
Search for
StructuresSwiss-model
DomainsInterPro

Human leukocyte histocompatibility complex DO (HLA-DO) is an intracellular, dimeric non-classical Major Histocompatibility Complex (MHC) Class II protein composed of α- and β-subunits which interact with HLA-DM in order to fine tune immunodominant epitope selection.[1] As a non-classical MHC Class II molecule, HLA-DO is a non-polymorphic accessory protein that aids in antigenic peptide chaperoning and loading, as opposed to it classical counterparts, which are polymorphic and involved in antigen presentation.[2][3] Though more remains to be elucidated about the function of HLA-DO, its unique distribution in the mammalian body, namely, the exclusive expression of HLA-DO in B cells, thymic medullary epithelial cells, and dendritic cells suggests that it may be of physiological importance and has inspired further research.[2][4] Moreover, HLA-DO is stable in complex with HLA-DM, and its exhibited instability in the absence of HLA-DM, as well as its evolutionary conservation, further denote its biological significance and potential to confer evolutionary benefits to its host.[5][6]

Discovery

Studies on HLA-DO transfected fibroblast cells lines and on the HLA-DO mouse homolog, H-2O, provide most of the current knowledge on the protein.[7] In 1985, the α- and β-chains were separately discovered, and in 1990, both chains were found to be co-expressed in one protein in H-2O.[5][6]

Function

Functionally, HLA-DO is believed to be negative modulator of HLA-DM; the binding of HLA-DO at the MHC Class II peptide-exchange catalysis site demonstrate that it acts as a competitive inhibitor.[1][5][4]

During infection, exogenous antigen is internalized by phagocytosis or receptor-mediated endocytosis, and processed in hydrolytic enzyme-containing compartments of increasing acidity.[1][6] Once the degraded antigen is 13-18 residues, it is ready to bind to MHC Class II molecules, which ultimately presents the antigen to T cells and class III molecules and progresses the immune response.[1] To bind to the MHC-Class II protein, HLA-DM catalyzes the exchange of CLIP, a protein occupying the binding groove of MHC Class II, with the antigenic oligopeptide.[1][6] HLA-DO remains strongly associates with HLA-DM throughout the catalyzed exchange.[2]

Structure

Before the three-dimensional structure of complexed HLA-DO was elucidated by X-ray crystallography, its crystal structure was modeled after homology studies to classical MHC Class II proteins.[3][6][8] Following crystallization of the protein, HLA-DO was found to be conformationally similar to classical MHC Class II protein, with alterations in the N-terminus.[3][7][8] The structure of the free HLA-DO protein, however, remains to be elucidated.[7]

References

  1. ^ a b c d e Owen JA, Punt J, Stranford SA, Jones PP, Kuby J (2013). Kuby immunology (7th ed.). New York: W.H. Freeman. ISBN 978-1-4641-1991-0. OCLC 820117219.
  2. ^ a b c Poluektov YO, Kim A, Sadegh-Nasseri S (September 2013). "HLA-DO and Its Role in MHC Class II Antigen Presentation". Frontiers in Immunology. 4: 260. doi:10.3389/fimmu.2013.00260. PMC 3756479. PMID 24009612.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ a b c Yin, Liusong; Stern, Lawrence J. (2013-10-17). "HLA-DM Focuses on Conformational Flexibility Around P1 Pocket to Catalyze Peptide Exchange". Frontiers in Immunology. 4. doi:10.3389/fimmu.2013.00336. ISSN 1664-3224. PMC 3797982. PMID 24146666.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  4. ^ a b Denzin, Lisa K. (2013-12-17). "Inhibition of HLA-DM Mediated MHC Class II Peptide Loading by HLA-DO Promotes Self Tolerance". Frontiers in Immunology. 4. doi:10.3389/fimmu.2013.00465. ISSN 1664-3224. PMC 3865790. PMID 24381574.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  5. ^ a b c Chen X, Jensen PE (June 2004). "The expression of HLA-DO (H2-O) in B lymphocytes". Immunologic Research. 29 (1–3): 19–28. doi:10.1385/IR:29:1-3:019. PMID 15181267.
  6. ^ a b c d e Adler, Lital N.; Jiang, Wei; Bhamidipati, Kartik; Millican, Matthew; Macaubas, Claudia; Hung, Shu-chen; Mellins, Elizabeth D. (2017-03-23). "The Other Function: Class II-Restricted Antigen Presentation by B Cells". Frontiers in Immunology. 8. doi:10.3389/fimmu.2017.00319. ISSN 1664-3224. PMC 5362600. PMID 28386257.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ a b c Mellins ED, Stern LJ (February 2014). "HLA-DM and HLA-DO, key regulators of MHC-II processing and presentation". Current Opinion in Immunology. 26: 115–22. doi:10.1016/j.coi.2013.11.005. PMC 3944065. PMID 24463216.
  8. ^ a b Pos, Wouter; Sethi, Dhruv K.; Wucherpfennig, Kai W. (2013-10). "Mechanisms of Peptide Repertoire Selection by HLA-DM". Trends in immunology. 34 (10): 495–501. doi:10.1016/j.it.2013.06.002. ISSN 1471-4906. PMC 3796002. PMID 23835076. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
Stub icon

This immunology article is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=HLA-DO&oldid=829309639"